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Reducing macrophage numbers alleviates temporomandibular joint ankylosis

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A Correction to this article was published on 18 November 2019

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Abstract

Temporomandibular joint (TMJ) ankylosis is a severe joint disease mainly caused by trauma that leads to a series of oral and maxillofacial function disorders and psychological problems. Our series of studies indicate that TMJ ankylosis development is similar to fracture healing and that severe trauma results in bony ankylosis instead of fibrous ankylosis. Macrophages are early infiltrating inflammatory cells in fracture and play a critical role in initiating fracture repair. We hypothesize that the large numbers of macrophages in the early phase of TMJ ankylosis trigger ankylosed bone mass formation and that the depletion of these macrophages in the early phase could inhibit the development of TMJ ankylosis. By analysing human TMJ ankylosis specimens, we found large numbers of infiltrated macrophages in the less-than-1-year ankylosis samples. A rabbit model of TMJ bony ankylosis was established and large numbers of infiltrated macrophages were found at 4 days post-operation. Local clodronate liposome (CLD-lip) injection, which depleted macrophages, alleviated the severity of ankylosis compared with local phosphate-buffered saline (PBS)-loaded liposome (PBS-lip) injection (macrophage number, PBS-lips vs. CLD-lips: 626.03 ± 164.53 vs. 341.4 ± 108.88 n/mm2; ankylosis calcification score, PBS-lips vs. CLD-lips: 2.11 ± 0.78 vs. 0.78 ± 0.66). Histological results showed that the cartilage area was reduced in the CLD-lip-treated side (PBS-lips vs. CLD-lips: 6.82 ± 4.42% vs. 2.71 ± 2.78%) and that the Wnt signalling regulating cartilage formation was disrupted (Wnt5a expression decreased 60% and Wnt4 expression decreased 73%). Thus, our study showed that large numbers of macrophages infiltrated during the early phase of ankylosis and that reducing macrophage numbers alleviated ankylosis development by reducing cartilage formation.

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  • 18 November 2019

    The article “Reducing macrophage numbers alleviates temporomandibular joint ankylosis”, written by Lu Zhao, E Xiao, Linhai He, Denghui Duan, Yang He, Shuo Chen, Yi Zhang and Yehua Gan, was originally published electronically on the publisher’s internet portal.

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Acknowledgements

We would also like to thank Dr. Jie Lei for her assistance with the radiological analysis.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81670959 and No. 81801000). The funders had no role in the design of the projects, performance of the experiments, analysis of the results or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China

    Lu Zhao, E Xiao, Linhai He, Denghui Duan, Yang He, Shuo Chen, Yi Zhang & Yehua Gan

  2. Laboratory of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China

    Lu Zhao, E Xiao, Denghui Duan, Yang He, Shuo Chen & Yi Zhang

  3. Peking University Hospital of Stomatology First Clinical Division, 37A Xishiku Street, Xicheng District, Beijing, 100034, China

    Linhai He

  4. Central Laboratory, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China

    Yehua Gan

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  1. Lu Zhao
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  2. E Xiao
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Contributions

L.Z. contributed to model building, sample collection, data acquisition and manuscript drafting; E.X. contributed to model building, data analysis and interpretation and critical revision of the manuscript; LH.H. assisted with the histological analysis and critical revision of the manuscript; DH.D. and Y.H. contributed to the sample collection and critical revision of the manuscript; S.C. assisted with the CBCT imaging evaluation; and Y.Z. and YH.G. contributed to the conception and design of the study and critical revision of the manuscript. All authors gave their final approval and agreed to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Yi Zhang or Yehua Gan.

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The authors declare that they have no conflicts of interest.

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Informed consent was obtained from all individual participants included in the study and this study was approved by the Ethics Committee of Peking University (IRB00001 05211002).

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All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All animal studies were performed in compliance with the regulations and guidelines of the Peking University institutional animal care committee (LA 2018016) and conducted according to AAALAC and IACUC guidelines.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Zhao, L., Xiao, E., He, L. et al. Reducing macrophage numbers alleviates temporomandibular joint ankylosis. Cell Tissue Res 379, 521–536 (2020). https://doi.org/10.1007/s00441-019-03087-7

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